Vulnerable plaque is a type of fatty buildup in an artery thought to be caused by inflammation. The plaque is covered by a thin, fibrous cap that upon rupture may lead to the formation of a blood clot and, ultimately, occlusion of the artery. Plaque rupture most often occurs in smaller arteries, such as the coronary arteries, which supply blood to the heart muscle. The occlusion of a coronary artery can lead to a heart attack.

"Vulnerable patients" are those who exhibit a high probability of dying of a heart attack within 12 months. Although most vulnerable patients have vulnerable plaques, not all people with vulnerable plaques will die of a heart attack. Vulnerable patients' risk of a heart attack is greater if their blood has an increased tendency to create clots or if their heart cells have a natural tendency to develop electrical instability; in patients with electrical instability, vulnerable plaques are more likely to rupture and cause cardiac arrest and sudden death.

The concept of vulnerable plaque is a major breakthrough in the field of cardiology. Until recently, physicians thought that the majority of heart attacks resulted from narrowing in a coronary artery that gradually and progressively slows blood flow until the artery is completely occluded. Researchers have since learned that even moderately occluded arteries with areas of vulnerable plaque are more likely to lead to heart attack.